scholarly journals Calcineurin complex isolated from T-cell acute lymphoblastic leukemia (T-ALL) cells identifies new signaling pathways including mTOR/AKT/S6K whose inhibition synergize with calcineurin inhibition to promote T-ALL cell death

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 45715-45729 ◽  
Author(s):  
Valeria Tosello ◽  
Valentina Saccomani ◽  
Jiyang Yu ◽  
Fulvio Bordin ◽  
Alberto Amadori ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Calcineurin Inhibition

scholarly journals CD 47 agonist peptide PKHB 1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

2018 ◽  
Vol 110 (1) ◽  
pp. 256-268 ◽  
Author(s):  
Ashanti Concepción Uscanga‐Palomeque ◽  
Kenny Misael Calvillo‐Rodríguez ◽  
Luis Gómez‐Morales ◽  
Eva Lardé ◽  
Thomas Denèfle ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cells ◽  
Immunogenic Cell Death ◽  
Agonist Peptide ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia

Leukemia ◽  
2014 ◽  
Vol 28 (12) ◽  
pp. 2324-2335 ◽  
Author(s):  
V Kumar ◽  
R Palermo ◽  
C Talora ◽  
A F Campese ◽  
S Checquolo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

2017 ◽  
Vol 18 (9) ◽  
pp. 1904 ◽  
Author(s):  
Deborah Bongiovanni ◽  
Valentina Saccomani ◽  
Erich Piovan
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Mitochondrial reactive oxygen species prime T-cell acute lymphoblastic leukemia to cell death by engaging the OMA1-OPA1 axis

2016 ◽  
Vol 1857 ◽  
pp. e115
Author(s):  
Micol Silic-Benussi ◽  
Gloria Scattolin ◽  
Ilaria Cavallari ◽  
Sonia Minuzzo ◽  
Giuseppe Basso ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 651
Author(s):  
Pablo Cruz ◽  
Ulises Ahumada-Castro ◽  
Galdo Bustos ◽  
Jordi Molgó ◽  
Daniela Sauma ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Lines ◽  
Mitochondrial Respiration ◽  
Lymphoblastic Leukemia ◽  
Specific Inhibitor ◽  
Prolonged Treatment ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Trisphosphate Receptor

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy whose chemoresistance and relapse persist as a problem despite significant advances in its chemotherapeutic treatments. Mitochondrial metabolism has emerged as an interesting therapeutic target given its essential role in maintaining bioenergetic and metabolic homeostasis. T-ALL cells are characterized by high levels of mitochondrial respiration, making them suitable for this type of intervention. Mitochondrial function is sustained by a constitutive transfer of calcium from the endoplasmic reticulum to mitochondria through the inositol 1,4,5-trisphosphate receptor (InsP3R), making T-ALL cells vulnerable to its inhibition. Here, we determine the bioenergetic profile of the T-ALL cell lines CCRF-CEM and Jurkat and evaluate their sensitivity to InsP3R inhibition with the specific inhibitor, Xestospongin B (XeB). Our results show that T-ALL cell lines exhibit higher mitochondrial respiration than non-malignant cells, which is blunted by the inhibition of the InsP3R. Prolonged treatment with XeB causes T-ALL cell death without affecting the normal counterpart. Moreover, the combination of XeB and glucocorticoids significantly enhanced cell death in the CCRF-CEM cells. The inhibition of InsP3R with XeB rises as a potential therapeutic alternative for the treatment of T-ALL.

scholarly journals Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5′AMP-Activated Kinase Inactivation

2021 ◽  
Vol 22 (12) ◽  
pp. 6384
Author(s):  
Valeria Tosello ◽  
Deborah Bongiovanni ◽  
Ludovica Di Martino ◽  
Cinzia Franchin ◽  
Paola Zanovello ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Metabolic Adaptation ◽  
Serum Starvation ◽  
Ampk Signaling ◽  
Compound C ◽  
Gli1 Expression ◽  
Cell Acute Lymphoblastic Leukemia

Numerous studies have shown that hedgehog inhibitors (iHHs) only partially block the growth of tumor cells, especially in vivo. Leukemia often expands in a nutrient-depleted environment (bone marrow and thymus). In order to identify putative signaling pathways implicated in the adaptive response to metabolically adverse conditions, we executed quantitative phospho-proteomics in T-cell acute lymphoblastic leukemia (T-ALL) cells subjected to nutrient-depleted conditions (serum starvation). We found important modulations of peptides phosphorylated by critical signaling pathways including casein kinase, mammalian target of rapamycin, and 5′AMP-activated kinase (AMPK). Surprisingly, in T-ALL cells, AMPK signaling was the most consistently downregulated pathway under serum-depleted conditions, and this coincided with increased GLI1 expression and sensitivity to iHHs, especially the GLI1/2 inhibitor GANT-61. Increased sensitivity to GANT-61 was also found following genetic inactivation of the catalytic subunit of AMPK (AMPKα1) or pharmacological inhibition of AMPK by Compound C. Additionally, patient-derived xenografts showing high GLI1 expression lacked activated AMPK, suggesting an important role for this signaling pathway in regulating GLI1 protein levels. Further, joint targeting of HH and AMPK signaling pathways in T-ALL cells by GANT-61 and Compound C significantly increased the therapeutic response. Our results suggest that metabolic adaptation that occurs under nutrient starvation in T-ALL cells increases responsiveness to HH pathway inhibitors through an AMPK-dependent mechanism and that joint therapeutic targeting of AMPK signaling and HH signaling could represent a valid therapeutic strategy in rapidly expanding tumors where nutrient availability becomes limiting.

scholarly journals Signaling pathways involved in the development of T-cell acute lymphoblastic leukemia

Haematologica ◽  
2008 ◽  
Vol 93 (4) ◽  
pp. 493-497 ◽  
Author(s):  
F. J.T. Staal ◽  
A. W. Langerak
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

Abstract 5533: Signaling pathways that regulate LMO2 oncogene expression in pediatric high risk T cell acute lymphoblastic leukemia

2017 ◽  
Author(s):  
Chandrika S. Gowda ◽  
Yali Ding ◽  
Chunhua Song ◽  
Malika Kapadia ◽  
Kimberly J. Payne ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Oncogene Expression ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis

Leukemia ◽  
2020 ◽  
Author(s):  
E. G. Garcia ◽  
A. Veloso ◽  
M. L. Oliveira ◽  
J. R. Allen ◽  
S. Loontiens ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
T Cell Signaling ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Cell Signaling Pathways

Targeting Signaling Pathways in T-cell acute lymphoblastic leukemia initiating cells

2014 ◽  
Vol 56 ◽  
pp. 6-21 ◽  
Author(s):  
Alberto M. Martelli ◽  
Annalisa Lonetti ◽  
Francesca Buontempo ◽  
Francesca Ricci ◽  
Pier Luigi Tazzari ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia
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